Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Abstract

Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

Keywords: Mesenchymal stem cell; Immunosuppression; Immunogenic; Autoimmunity; Cell-based therapy

Core tip: Mesenchymal stem cells (MSCs) comprise a mixture of different stromal cell types that display remarkable pleiotropic properties, including those of anti-apoptosis, angiogenesis, growth factor production, anti-fibrosis, and chemo-attraction. It is because of these diverse biological properties that these cells have been intensively studied in the hopes of their utilization as a platform of cellular therapy in disease settings. Early experimental and preclinical studies focused on their stem cell renewal, differentiation, and regenerative properties for potential use in degenerative diseases of mesenchymal origin. Afterwards, MSCs were found to increase the success of bone marrow transplantation, reduce rejection of engrafted tissues, and display remarkable anti-inflammatory properties. Currently, much work centers on the immune-modulatory facets of MSCs, especially in reducing inflammation and suppressing immune cell function in preclinical injury and autoimmune disease settings. However, emerging reports suggest a multifunctional quality to MSC immune-modulation. This review dissects MSC manipulation of immune responses, which result in either immunosuppression or immuno-stimulation.